Our aim is to answer the following questions: 1. How much detectable allelic variation is present in genes coding for different types of polypeptides in natural populations of Drosophila? 2. Does the observed allelic variation respond to natural selection? 3. What is the nature of genetic changes that occur at different levels of speciation? This work will be done with D. pseudoobscura, D. persimilis and D. miranda. For further allelic identifications among allelic proteins and enzymes sharing the same electrophoretic mobility, we will carry out isoelectric focussing in gels and denaturation studies with heat, urea and guanidine hydrochloride. In addition, we will examine relative levels of enzymes and proteins in different isogenic lines and the capacity of different allozymes to form hybrid enzymes. Genetic analysis will be done to show that the observed differences in proteins from different isogenic lines are due to alleles. Kinetic studies with several partially purified enzymes will be carried out. We will study polymorphism in ribosomal proteins and histones by gel electrophoresis. Pattern of proteins and enzymes from different developmental stages will be studied by electrophoresis, in order to find out if any polymorphisms for different periods of appearance and disappearance of proteins exist. In order to demonstrate the action of natural selection on allelic variation, we will perform several different population cage experiments and will study linkage correlations among several linked loci in chromosomes derived from natural populations and population cages.